None listed
Conditions
Interventions
Group 1 Type of group
TAK-559 32 mg orally for 26 weeks
Group name:Group 3 Type of group
Placebo orally for 26 weeks
Sponsors
TAKEDA PHARMACEUTICALS,
Eligibility
Inclusion criteria
Inclusion criteria: • Male or female patients diagnosed with type 2 diabetes mellitus according to the diagnostic criteria of the American Diabetes Association (ADA) (Appendix B) who are receiving a stable dose of an AAO as monotherapy ( administration of TZD and PPAR agonists should be discontinued 3 months before Randomization) before Selection A. • Patients between 25 and 75 years of age, inclusive, in Selection A. • Patients with an HbA1c level greater than or equal to 8.0% and less than or equal to 10.0% in Selection B. • Patients with an FPG level greater than or equal to 126 mg / dl (7.0 mmol / L) in Selection B. • Patients should be receiving a stable dose of at least 1,000 mg per day of metformin for at least 30 days before Screening B. • Patients with a stable SMBG level or who would have worsened with the administration of metformin. Patients who do not qualify before Selection B may continue the selection period (see Section 8.1.4). • Patients with an LDL level lower than 160 mg / dl (4.1 mmoI / 1) in Selection A. • Patients with a body mass index (IMG) less than or equal to 45 kg / m2 in Selection A. • Patients who are willing to receive advice from the investigator or the designated person to follow an individualized diet to maintain weight during the study period. • Patients with evidence of the ability to secrete insulin demonstrated by a concentration of C peptide greater than or equal to 1.5 mg / ml (0.50 nmol / L) in Selection A, and if necessary, after repeating the test in the Selection B. If the patient is between 25 and 29 years of age, an additional test will be performed to determine the concentration of C-peptide in Selection B. • Patients willing to perform SMBG daily throughout the study. • Patients with a normal level of thyroid stimulating hormone (TSH) of less than 5.5 iiIU / ml (5.5 mlU / I) and greater than or equal to 0.35 fU / ml (0.35 mIU / 1) in the Selection A. If the TSH level of! patient is greater than 5.5 plU / ml (5.5 mIU / 1), the level of free T4 can be determined. If the level of free T4 is within the normal limits of that patient, the patient can remain in the study. • Patients in good health according to the criteria of a doctor (ie, through the study of the clinical history and physical examination [EF]), regardless of the diagnosis of type 2 diabetes mellitus. • Patients whose laboratory clinical fasting analyzes are within the normal reference range for laboratory analyzes or whose results are not considered clinically significant by the investigator prior to Randomization. • Post-menopausal women (defined as 2 years without menstrual cycles at least), surgically sterile or using an adequate contraceptive method (suitable contraceptive methods are: hormonal contraceptives, double barrier methods and / or intrauterine devices; contraceptive methods NOT acceptable are: abstinence, vasectomy and sterility of the couple), that are not breastfeeding and women of childbearing age whose pregnancy test has had a negative result in Selection A and before receiving the first dose of the study medication.
Exclusion criteria
Exclusion criteria: • Patients diagnosed with diabetes mellitus type 1, hemochromatosis or with a history of ketoacidosis. • Patients with diseases that invalidate the results of the HbA1c level (eg, hemolytic states, hemoglobinopathies). • Patients who have received any of the medications not allowed after Selection A • Patients who received PPAR, TZD, nicotinic acid or fibrate agonists within 3 months prior to Randomization. • Patients who have received systemic corticosteroids within the month prior to Randomization. • Patients with a history of myocardial infarction, coronary angioplasty or aortocoronary bypass, unstable angina pectoris, transient ischemic attacks, clinically significant abnormal ECG or cerebrovascular accident registered during the 6 months prior to Screening A. Patients will not be eligible if they present a Clinically significant abnormal ECG in the selection. • Patients who have undergone abdominal, thoracic or vascular surgery during the 6 months prior to Screening A, which, according to the investigator´s criteria, justify the exclusion of the patient from this study. • Patients with creatine kinase (CPK) values ​​more than 3 times higher than the upper limit of the normal range (LSN) in Selection A. The CPIC value, if elevated, can be reassessed before Randomization . • Patients with persistent unexplained microscopic or macroscopic hematuria or a history of bladder cancer. In case of non-explainable hematuria determined by the microscopic presence of more than 3 erythrocytes (RBC) per high power field (HPF) in 2 separate analyzes within 14 days (according to central laboratory report), the patient should be referred to a urologist to perform additional follow-up in accordance with the recommendations for the clinical practice of the AUA [7]. • Patients with a triglyceride level greater than 500 mg / dl (5.6 mmol / L) in Selection A. • Patients to whom the permitted lipid-lowering medication (dose or drug) has been modified within 2 months prior to Randomization, if applicable. The patient must maintain a stable dose throughout the study. If necessary, the dose may be reduced with the prior approval of the sponsor. • Patients who have donated blood and / or received blood products within 3 months prior to Randomization. • Patients with a history of drug abuse (defined as the consumption of illicit drugs) or a history of excessive alcohol consumption (defined as regular or daily consumption of more than 4 alcoholic beverages) within 2 years prior to Randomization or a positive test of drug detection in urine. Patients with positive urine drug or alcohol test results that can be justified by a clinically relevant reason may continue in the selection process. • Patients with a systolic blood pressure (BP) greater than 140 mm Hg or a diastolic BP greater than 95 mm Hg in Selection B. • Patients with significant cardiovascular disease including, without limitation, categories III or IV of the Functional (Cardiac) Classification of the New York Heart Association (NYHA) (Appendix C). • Patients with a history of cancer, other than basal cell carcinoma or skin-stage squamous cell carcinoma that has not remitted within 5 years prior to Randomization. • Patients with a level of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 greater than the upper limit of the normal range, active liver disease or jaundice in Selection A.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Change from baseline in the HbA1c level between the treatment groups that will receive TAK-559 and the group that will receive the placebo in Week 26 Measure:Change from baseline in the HbA1c level Timepoints:Week 26 | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Change from baseline in C-peptide, fasting plasma glucose, free fatty acids Measure:Change from baseline in C-peptide, fasting plasma glucose, free fatty acids Timepoints:Weeks 2, 4, 8, 12, 16, 20 and Final Visit ; Outcome name:Change from baseline in glycosylated hemoglobin, high-density lipoprotein, inflammation marker C-reactive protein. Measure:Change from baseline in glycosylated hemoglobin, high-density lipoprotein, inflammation marker C-reactive protein. Timepoints:Weeks 2, 4, 8, 12, 16 and 20 ; Outcome name:Change from baseline in inflammation marker Interleukin-6, low-density lipoprotein, serum insulin, thrombosis marker fibrinogen, thrombosis marker plasminogen activator inhibitor-1 Measure:Change from baseline in inflammation marker Interleukin-6, low-density lipoprotein, serum insulin, thrombosis marker fibrinogen, thrombosis marker plasminogen activator inhibitor-1 Timepoints:Weeks 4, 12, 16, 20 and Final Visit ; Outcome name:Change from baseline in total cholesterol, triglycerides, urinary albumin to creatinine ratio, very-low-density lipoprotein. Measure:Change from baseline in total cholesterol, triglycerides, urinary albumin to creatinine ratio, very-low-density lipoprotein. Timepoints:Weeks 12, 16, 20 and Final Visit | — |
Outcome results
None listed